Fucose (6-deoxy-galactose) is one of the examples of so-called rare monosaccharides. Fucose is found in a wide variety of natural products from many different sources, in both D-form and L-form. Fucose occurs in several human milk oligosaccharides, in eggs of sea urchins and in frog spawn. L-Fucose is present in polysaccharides from plants such as seaweed (in the form of fucoidan, sulphated fucose polymer), gum tragacanth, potato, kiwi fruit, soybean, winged bean varieties, canola, etc. In plant material, fucose is typically associated with plant polysaccharides, which are often highly branched structures having L-fucopyranosyl units either at the ends of or within the polysaccharide chains. Both N-and O-glycosyl chains of human or animal glycoproteins may contain L-fucose bound to the termini of the carbohydrate chains. Furthermore, extracellular polysaccharides from various bacteria, fungi and micro-algae also contain L-fucose.
Interest in L-fucose has recently increased because of its potential in the medical field in treating various disease conditions, such as tumors, inflammatory conditions and disorders relating to the human immune system. L-fucose has also applications in the cosmetic field, for instance as skin moisturizing, skin regenerating and anti-aging agent or for prevention epidermal (skin) inflammation.
Although enzyme- or microbe-assisted production of fucose is known from the art, L-fucose is usually obtained from natural sources or produced via chemical modifications of common monosaccharides (see a review on L-fucose: P. T. Vanhooren et al. J. Chem. Technol. Biotechnol. 74, 479 (1999) and references cited therein).
Regarding fucose production from natural sources, fucose containing oligosaccharides that can be isolated from biomass, preferably from algae e.g. by extraction, are hydrolyzed to provide a complex mixture containing fucose as well as related sugars and/or derivatives thereof. Recovery of fucose from the mixture typically needs sophisticated separation techniques such as treatment or chromatography with anion or cation exchange resins, dialysis, fractional crystallization, etc., depending on the nature of the accompanying sugars or sugar-related compounds. For example the article of P. Saari et. al. (J. Liquid Chrom. Rel. Tech. 32, 2050 (2009)) and the international application WO 2005/040430 disclose chromatographic separation of spent liquor obtained from pulping processes by means of cation and/or anion exchange resins or combination thereof. The resulting syrup, which is enriched in fucose (at least 72%) and still contains rhamnose, methyl α-D-xylopyranoside, xylose, arabinose and galactose as well, was then subjected to fractional crystallization from aqueous ethanol to obtain fucose.
With regard to chemical synthesis of L-fucose, chemical modifications of common monosaccharides like L-galactose, D-galactose, L-arabinose, D-glucose, D-mannose and L-rhamnose have been published. One of the most elegant processes (J. Defaye et al. Carbohydr. Res. 126, 165 (1984), Scheme 1., R=Me) starts from L-rhamnose which was first converted to methyl rhamnoside (A) then protected as 2,3-O-isopropylidene acetal (B).

The free 4-OH group was oxidized resulting in the corresponding hexulose (C) followed by borohydride reduction and acidic hydrolysis giving rise to 6-deoxy-L-talose. Epimerization of the latter in the presence of molybdic acid, known as Bílik reaction (see L. Petru{hacek over (s)} et al. Topics Curr. Chem. 215, 15 (2001) and references cited therein), resulted in an equilibrium between 6-deoxy-L-talose and its 2-epimer L-fucose wherein L-fucose was favoured (7:1). As L-fucose forms weaker complex with cations than 6-deoxy-L-talose, separation of these sugars could be effected by means of column chromatography with a cation exchange resin in Ca- or Ba-form. The same interconversion could be performed under microwave irradiation instead of conventional conductive heating and the epimers were separated on a column filled with DOWEX 50W X8 in Ba-form (Z. Hricovíniová Tetrahedron: Asymmetry 20, 1239 (2009)).
The main drawback of the above-mentioned procedures is the unavoidable chromatographic separation in order either to get the pure substance or to obtain at least a mixture that is enriched in the target compound but still contains undesired derivatives. Although repeated chromatographic separation may result in the improvement of the purity, its high cost and relatively long technological time to handle the feed solution and the column packing, to carry out the separation and optionally to regenerate the packing, especially in large or industrial scale, can be disadvantageous and/or cumbersome.
Crystallization or recrystallization is one of the simplest and cheapest methods to isolate a product from a reaction mixture, separate it from contaminations and obtain pure substance. Isolation or purification that uses crystallization makes the whole technological process robust and cost-effective, thus it is advantageous and attractive compared to other procedures.